MicroRNAs (miRNAs) role in hypertension: pathogenesis and promising therapeutics.

Background: MicroRNAs (miRNAs) are small, non-coding RNA molecules that play a crucial role in regulating various cellular processes, including cell proliferation, differentiation, apoptosis, and disease development. Recent studies have highlighted the importance of miRNAs in the development and progression of essential hypertension, a common form of high blood pressure that affects millions of individuals worldwide. The molecular mechanisms by which miRNAs regulate hypertension are complex and multifaceted. MiRNAs target the 3' untranslated regions of mRNA molecules, thereby regulating the synthesis of specific proteins involved in cardiovascular function. For instance, miRNAs are known to regulate the expression of genes involved in blood vessel tone, cardiac function, and inflammation. The growing body of research on miRNAs in hypertension has highlighted their potential as therapeutic targets for managing this condition. Studies have shown that miRNA-based therapies can modulate the expression of key genes involved in hypertension, leading to improvements in blood pressure and cardiovascular function. However, more research is needed to fully understand the mechanisms of miRNA-mediated hypertension and to develop effective therapeutic strategies. Conclusions: In summary, this review highlights the current understanding of the role of miRNAs in essential hypertension, including their molecular mechanisms and potential therapeutic applications. Further research is needed to fully understand the impact of miRNAs on hypertension and to develop new treatments for this common and debilitating condition.

Association of serum leptin and ghrelin levels with smoking status on body weight: a systematic review and meta-analysis.

Background and aims: Smoking cigarettes is a major global health problem that affects appetite and weight. The aim of this systematic review was to determine how smoking affected plasma leptin and ghrelin levels. Methods: A comprehensive search of PubMed, Scopus, Web of Science, and Ovid was conducted using a well-established methodology to gather all related publications. Results: A total of 40 studies were included in the analysis of 11,336 patients. The overall effect showed a with a mean difference (MD) of -1.92[95%CI; -2.63: -1.20] and p = 0.00001. Subgroup analysis by study design revealed significant differences as well, but with high heterogeneity within the subgroups (I2 of 82.3%). Subgroup by sex showed that there was a significant difference in mean difference between the smoking and non-smoking groups for males (MD = -5.75[95% CI; -8.73: -2.77], p = 0.0002) but not for females (MD = -3.04[95% CI; -6.6:0.54], p = 0.10). Healthy, pregnant, diabetic and CVD subgroups found significant differences in the healthy (MD = -1.74[95% CI; -03.13: -0.35], p = 0.01) and diabetic (MD = -7.69[95% CI, -1.64: -0.73], p = 0.03). subgroups, but not in the pregnant or cardiovascular disease subgroups. On the other hand, the meta-analysis found no statistically significant difference in Ghrelin serum concentration between smokers and non-smokers (MD = 0.52[95% CI, -0.60:1.63], p = 0.36) and observed heterogeneity in the studies (I2 = 68%). Conclusion: This study demonstrates a correlation between smoking and serum leptin/ghrelin levels, which explains smoking's effect on body weight. Systematic review registration: https://www.crd.york.ac.uk/ prospero/display_record.php, identifier (Record ID=326680).

Dabrafenib plus trametinib versus anti-PD-1 monotherapy as adjuvant therapy in BRAF V600-mutant stage III melanoma after definitive surgery: a multicenter, retrospective cohort study.

Background: Both dabrafenib/trametinib (D/T) and anti-PD-1 monotherapy (PD-1) are approved adjuvant therapies for patients with stage III BRAF V600-mutant melanoma. However, there is still a lack of head-to-head comparative data. We aimed to describe efficacy and toxicity outcomes for these two standard therapies across melanoma centers. Methods: This multicenter, retrospective cohort study was conducted in 15 melanoma centers in Australia, China, Germany, Italy, Japan, UK, and US. We included adult patients with resected stage III BRAF V600-mutant melanoma who received either adjuvant D/T or PD-1 between Jul 2015 and Oct 2022. The primary endpoint was relapse-free survival (RFS). Secondary endpoints included overall survival (OS), recurrence pattern and toxicity. Findings: We included 598 patients with stage III BRAF V600-mutant melanoma who received either adjuvant D/T (n = 393 [66%]) or PD-1 (n = 205 [34%]) post definitive surgery between Jul 2015 and Oct 2022. At a median follow-up of 33 months (IQR 21-43), the median RFS was 51.0 months (95% CI 41.0-not reached [NR]) in the D/T group, significantly longer than PD-1 (44.8 months [95% CI 28.5-NR]) (univariate: HR 0.66, 95% CI 0.50-0.87, P = 0.003; multivariate: HR 0.58, 95% CI 0.39-0.86, P = 0.007), with comparable OS with PD-1 (multivariate, HR 0.90, 95% CI 0.48-1.70, P = 0.75). Similar findings were observed using a restricted-mean-survival-time model. Among those who experienced recurrence, the proportion of distant metastases was higher in the D/T cohort. D/T had a higher incidence of treatment modification due to adverse events (AEs) than PD-1, but fewer persistent AEs. Interpretation: In patients with stage III BRAF V600-mutant melanoma post definitive surgery, D/T yielded better RFS than PD-1, with higher transient but lower persistent toxicity, and comparable OS. D/T seems to provide a better outcome compared with PD-1, but a longer follow-up and ideally a large prospective trial are needed. Funding: Dr. Xue Bai was supported by the Beijing Hospitals Authority Youth Programme (QMS20211101) for her efforts devoted to this study. Dr. Keith T. Flaherty was funded by Adelson Medical Research Foundation for the efforts devoted to this study.

Deep brain stimulation for substance use disorder: a systematic review and meta-analysis.

Objective: Substance use disorder (SUD) is a significant public health issue with a high mortality rate. Deep brain stimulation (DBS) has shown promising results in treating SUD in certain cases. In this study, we conducted a meta-analysis to evaluate the efficacy of DBS in the treatment of SUD and reduction of relapse rates. Methods: We performed a thorough and methodical search of the existing scientific literature, adhering to the PRISMA guidelines, to identify 16 original studies that fulfilled our inclusion criteria. We used the evidence levels recommended by the Oxford Centre for Evidence-Based Medicine to assess bias. The R version 4.2.3 software was utilized to calculate the mean effect size. We estimated study heterogeneity by employing tau2 and I2 indices and conducting Cochran's Q test. Results: The results showed that DBS treatment resulted in a significant improvement in the clinical SUD scales of patients, with an average improvement of 59.6%. The observed relapse rate was 8%. The meta-analysis estimated a mean effect size of 55.9 [40.4; 71.4]. Heterogeneity analysis showed a large degree of heterogeneity among the included studies. Subgroup and meta-regression analysis based on age and SUD type suggested that DBS may be more effective for patients above 45 years of age, and for alcohol and opioid addiction compared to nicotine addiction. Conclusion: The current literature suggests that DBS has a moderate effect on SUD symptoms. However, the limited number of studies and small sample size indicate that more research is needed to better understand the factors that influence its effectiveness.

Endocardial-Epicardial Catheter Ablation Versus Endocardial Catheter Ablation Alone for Ventricular Arrhythmia in Patients With Structural Heart Disease (Meta-Analysis of Reconstructed Time-to-Event Data).

Endocardial-epicardial (Endo-epi) catheter ablation (CA) has been shown to reduce the rate of ventricular arrhythmia (VA) ablation in patients with structural heart disease (SHD). However, the effectiveness of this technique compared with endocardial (Endo) CA alone remains uncertain. This meta-analysis aims to compare the effectiveness of Endo-epi versus Endo alone in reducing the risk of VA recurrence in patients with SHD. We searched PubMed, Embase, and Cochrane Central Register with a comprehensive strategy. We used reconstructed time-to-event data to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for VA recurrence accompanied by at least one Kaplan-Meier curve for ventricular tachycardia recurrence. Our meta-analysis included 11 studies with a total of 977 patients. Endo-epi had a significantly lower risk of VA recurrence compared with those treated with Endo alone (HR 0.43, 95% CI 0.32 to 0.57, p <0.001). Subgroup analysis based on the type of cardiomyopathy revealed that patients with arrhythmogenic right ventricular cardiomyopathy and ischemic cardiomyopathy (ICM) benefited significantly from Endo-epi in reducing the risk of VA recurrence (HR 0.835, 0.55 to 0.87, p <0.021). However, there was no significant difference with non-ICM (HR 0.440, 0.55 to 0.87, p <0.33). The analysis of conditional survival showed that patients who remained free of VA recurrence for 5 years after the procedure had a very low probability of developing VA recurrence thereafter. In conclusion, Endo-epi CA is more effective than Endo CA alone in reducing the risk of VA recurrence in patients with SHD, especially those with arrhythmogenic right ventricular cardiomyopathy and ICM.

Long-term sequelae of COVID-19 (myalgic encephalomyelitis): An international cross-sectional study.

BACKGROUND: As a result of prolonged effects on multiple organs, recovery from COVID-19 caused by SARS-CoV-2 cannot be verified. This study seeks to understand chronic and acute long-term symptoms of COVID-19 lasting from a few weeks after diagnosis. The study also aims to gain insight into prevalence of chronic fatigue syndrome/myalgic encephalomyelitis, a potentially comorbid condition for several months after the infection, in addition to taking a broad perspective on rare symptoms that may have developed during or after the infection. STUDY DESIGN: Cross-sectional questionnaire\descriptive study. METHODS: The questionnaire was developed to assess the long-term effects of the global pandemic of COVID-19 using DePaul Symptom Questionnaire-2. The DePaul Symptom Questionnaire, Patient Health Questionnaire, and other symptoms that have been introduced by literature review. DISCUSSION: A large cohort of people from all over the world will be examined to understand the differential effects of people who have experienced COVID-19, as well as the potential occurrence of ME. In total, 20,000 COVID patients are expected to be included in the study by Sep 1, 2022. Patients who have experienced COVID-19 will be asked about their persistent symptoms from 1 week up to more than 6 months after catching or recovery from the infection.

Amoebic Hepato-Pericardial Fistula Complicating Amoebic Liver Abscess Treated With Pericardiotomy: A Case Report.

Parasitic infections like amoebiasis are often asymptomatic in the tropics, but the invasive disease can cause an amoebic liver abscess. During pericardiocentesis, amoebiasis is more noticeable in left lobe abscesses with chocolate-like pus drainage. Here, we present an unusual amoebic liver abscess that erupted into the pericardial cavity via a diaphragmatic fistula. An emergency pericardiotomy was performed to relieve cardiac tamponade, and the liver abscess was evacuated through a diaphragmatic rent identified during the surgery. This illustrates the catastrophic complications of an amoebic liver abscess.

Is there a need to be worried about the new monkeypox virus outbreak? A brief review on the monkeypox outbreak.

The Monkeypox virus (MPXV) is a double-stranded DNA virus related to the orthopoxvirus genus in the family of poxviridae. MPXV is endemic in central and Western African countries. There have been several outbreaks of MPXV in non-endemic countries since it was discovered in 1958 in lab monkeys. The current spread of MPXV is different from previous outbreaks, raising concerns about its potential to cause pandemics around the world. In order to reduce the spread of the disease, several countries imposed different preventive measures. The MPXV virus is believed to be transmitted either through wild animals, such as rodents or through infected individuals. Every year, Africa experiences a few thousand cases, mostly in the west and central regions. The number of cases outside Africa has previously been limited to a handful associated with travel to Africa or with the importation of infected animals. In this narrative review, we will discuss the clinical diagnosis, transmission, distribution, treatment, and prevention of the recent monkeypox outbreak around the world.

Combination of palbociclib with adjuvant endocrine therapy for treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer: An experience at two cancer centers in Saudi Arabia.

The addition of palbociclib (a cyclin-dependent kinase 4/6 inhibitor) to endocrine therapy (ET) has been shown to significantly improve progression-free survival (PFS) and overall survival (OS) among patients with hormone receptor-positive (HR+) advanced breast cancer. The current study presents the local experience of using palbociclib at two cancer centers in Saudi Arabia. Electronic data of patients with metastatic HR+ and human epidermal growth factor receptor 2-negative breast cancer who progressed after prior ET and received at least one cycle of palbociclib plus ET, were retrospectively reviewed. A total of 97 patients were identified, and their data were included in the analysis. The median age of the patients was 55 years. Patients were heavily pretreated in the metastatic setting (55% received systemic chemotherapy and 49% received two or more lines of prior ET). In total, 29 (30%) and 50 (52%) patients achieved an objective response and clinical benefit, respectively. The median follow-up time was 31.0 months [95% confidence interval (CI), 16.9-44.9] and the median PFS time was 16.3 months (95% CI, 11.4-21.2), with 58% of patients remaining progression-free at 12 months. Upon multivariate regression analysis, liver involvement was the only significant independent variable that predicted a greater risk of progression or death (hazard ratio, 2.32; 95% CI, 1.22-4.40; P=0.010). The median OS time was 19.6 months (95% CI, 18.1-20.9), with 12- and 24-month OS rates of 75 and 30%, respectively. Overall, real-world data showed that administration of palbociclib in combination with ET in patients with advanced HR+ breast cancer achieved a favorable outcome that was comparable to that reported in clinical trials.

Systematic analysis of authorship demographics in global surgery.

BACKGROUND: Global surgery has recently gained prominence as an academic discipline within global health. Authorship inequity has been a consistent feature of global health publications, with over-representation of authors from high-income countries (HICs), and disenfranchisement of researchers from low-income and middle-income countries (LMICs). In this study, we investigated authorship demographics within recently published global surgery literature. METHODS: We performed a systematic analysis of author characteristics, including gender, seniority and institutional affiliation, for global surgery studies published between 2016 and 2020 and indexed in the PubMed database. We compared the distribution of author gender and seniority across studies related to different topics; between authors affiliated with HICs and LMICs; and across studies with different authorship networks. RESULTS: 1240 articles were included for analysis. Most authors were male (60%), affiliated only with HICs (51%) and of high seniority (55% were fully qualified specialist or generalist clinicians, Principal Investigators, or in senior leadership or management roles). The proportion of male authors increased with increasing seniority for last and middle authors. Studies related to Obstetrics and Gynaecology had similar numbers of male and female authors, whereas there were more male authors in studies related to surgery (69% male) and Anaesthesia and Critical care (65% male). Compared with HIC authors, LMIC authors had a lower proportion of female authors at every seniority grade. This gender gap among LMIC middle authors was reduced in studies where all authors were affiliated only with LMICs. CONCLUSION: Authorship disparities are evident within global surgery academia. Remedial actions to address the lack of authorship opportunities for LMIC authors and female authors are required.

Efficacy of Regorafenib in Metastatic Colorectal Cancer: A Multi-institutional Retrospective Study.

BACKGROUND: Regorafenib is a multi-kinase inhibitor approved for treatment of refractory advanced colorectal cancer. It was found in the clinical trials to have a modest benefit and significant toxicity. Our aim was to assess the outcome in our local clinic practice. PATIENTS AND METHODS: Records of patients with confirmed colorectal cancer treated with regorafenib were reviewed. Clinical, pathological, and molecular data were collected. Efficacy and factors of possible prognostic significance were analyzed. RESULTS: A total of 78 patients with metastatic colorectal cancer were treated with regorafenib from February 2014 to February 2016 in 4 different institutions (median age: 50.5 years; male: 40 [51.3%]; KRAS mutant: 41 [52%]; right colonic primary: 18 [23%]). A total of 52 patients (66.7%) had Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1, whereas in 25 patients (32.1%) it was >1. In total, 58 patients (74%) had dose reduction. No patient achieved objective response, 15 patients (19%) achieved stable disease, and 56 patients (72%) had progressive disease. With a median follow-up of 6.5 months, the median progression-free survival was 2.8 months (95% confidence interval [CI], 2.5-3.3) and overall survival was 8.0 months (95% CI, 6.2-9.7). Only performance status of ⩽1 had a statistically significant impact on progression-free survival and overall survival in both univariate and multivariate analyses. CONCLUSIONS: Regorafenib in our clinical practice has equal efficacy to reported data from pivotal registration trials. Our data suggest that performance status is the most important prognostic factor in patients treated with regorafenib, suggesting a careful selection of patients.

Antagonist protocol versus clomiphene in unexplained infertility: A randomized controlled study.

OBJECTIVE: The primary purpose of this randomized controlled trial study was to compare clinical pregnancy rates and ovulation parameters in female patients of unexplained infertility undergoing intrauterine insemination (IUI) using an antagonist protocol versus a conventional clomiphene citrate protocol. MATERIALS AND METHODS: This was a multicenter parallel randomized controlled, open-label trial. A central randomization center used computer generated tables to allocate treatments. We conducted the study in two centers: Saudi Center and Samir Abbas and Assisted Reproductive Techniques Center of Cairo University, Cairo, Egypt between January 2011 and January 2014. Six hundred and twenty-two couples with unexplained infertility were randomized into two equal groups with 27 excluded after randomization: the antagonist protocol group and the clomiphene group. Antagonist protocol: human menopausal gonadotropins were given to 298 patients from Day 2 to reach a dominant follicle of 18-22 mm, intramuscularly. Then, orgalutrone (0.25 mg) was subcutaneously started from Day 6 or Day 7 until the day of human chorionic gonadotropins (hCG; that was given in the dose of 10,000 IU, intramuscularly) when follicles reached 18-22 mm. Afterward, the IUI of 0.5 mL was done from 34 hours to 36 hours using IUI catheter without guidance of ultrasonography and with an empty urinary bladder. The clomiphene citrate protocol was clomiphene citrate given 100 mg/d to 297 patients from Day 2 to Day 6 and follow up until day of hCG. The clinical pregnancy rate detected with ultrasound confirmed fetal heart pulsations at 6-weeks' gestation (4 weeks after IUI). The number of dominant follicles, level of serum estradiol, and luteinizing hormone at the day of hCG injection and the incidence of twin or triplet pregnancies in both groups were secondary outcome measures. RESULTS: The clinical pregnancy rate in the antagonist protocol group was significantly (p < 0.001) higher than in the clomiphene group. It was 80 patients (27%) in the antagonist protocol group versus 41 patients (14%) in the clomiphene group. The mean number of dominant follicles was significantly (p < 0.001) greater in the antagonist protocol group (4.36 ± 1.36 dominant follicles) compared with the clomiphene group (2.71 ± 0.96 dominant follicles). In addition, the rate of twin pregnancies was 15 cases in the antagonist protocol group versus six cases only in the clomiphene group (p = 0.047). The luteinizing hormone also was significantly lower in the antagonist group (2.1 ± 1.3) compared with that in the clomiphene group (9.5 ± 3.6). CONCLUSION: IUI clinical pregnancy rates were significantly higher by antagonist protocol.

Wegener's granulomatosis: the current understanding.

Wegener's granulomatosis (WG) is a rare systemic disease characterized by necrotizing granulomatous inflammation of the upper and lower respiratory tract, glomerulonephritis and vasculitis. It occurs as a limited form or generalized form and usually presents with nonspecific symptoms in its early stages, making the diagnosis of this disease more elusive. Strawberry gingivitis is the most common oral manifestation and is characteristic. Prompt recognition of this early manifestation is of utmost importance for the institution of early treatment, thereby avoiding serious complications. The present paper selectively reviews the literature regarding the current status of WG with respect to diagnosis, laboratory features, and treatment.